Knocking out barriers to engineered cell activity

@article{Hamilton2020KnockingOB,
  title={Knocking out barriers to engineered cell activity},
  author={Jennifer R. Hamilton and Jennifer A. Doudna},
  journal={Science},
  year={2020},
  volume={367},
  pages={976 - 977}
}
CRISPR-Cas9 gene-edited T cells show safety and long-term engraftment in humans Engineered T cell therapies are revolutionizing cancer treatment by achieving long-lasting remission in blood-related cancers, such as leukemia and lymphoma. These therapies involve removal of patient T cells, “reprogramming” them to attack cancer cells, and then transferring them back into the patient. Targeted gene inactivation (knockout) using CRISPR-Cas9 can enhance T cell activity (1, 2) and has the potential… 
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References

SHOWING 1-10 OF 11 REFERENCES
CRISPR-engineered T cells in patients with refractory cancer
TLDR
This first-in-human, phase 1 clinical trial was designed to test the safety and feasibility of multiplex CRISPR-Cas9 gene editing of T cells from patients with advanced, refractory cancer and found the persistence of the T cells expressing the engineered TCR was much more durable than in three previous clinical trials during which T cells were infused.
Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition
TLDR
Gene-disrupted allogeneic CAR and TCR T cells could provide an alternative as a universal donor to autologous T cells, which carry difficulties and high production costs.
CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells
TLDR
Improved therapeutic efficacy of Cas9-edited CAR T cells is demonstrated and the potential of precision genome engineering to enhance next-generation cell therapies is highlighted.
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
TLDR
It is demonstrated that directing a CD19-specific CAR to the T- cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia.
Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells
  • A. Seki, S. Rutz
  • Biology, Medicine
    The Journal of experimental medicine
  • 2018
TLDR
An optimized approach for Cas9/RNP transfection of primary mouse and human T cells without TCR stimulation that results in near complete loss of target gene expression at the population level, mitigating the need for selection is described.
Reprogramming human T cell function and specificity with non-viral genome targeting
TLDR
A non-viral strategy to introduce large DNA sequences into T cells enables the correction of a pathogenic mutation that causes autoimmunity, and the replacement of an endogenous T-cell receptor with an engineered receptor that can recognize cancer antigens.
Identification of preexisting adaptive immunity to Cas9 proteins in humans
TLDR
Together, these data demonstrate that there are preexisting humoral and cell-mediated adaptive immune responses to Cas9 in humans, a finding that should be taken into account as the CRISPR–Cas9 system moves toward clinical trials.
A Pilot Trial of the Combination of Transgenic NY-ESO-1–reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab
TLDR
ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipILimumab.
CAR T cell immunotherapy for human cancer
TLDR
Opportunities and challenges for entering mainstream oncology that presently face the CAR T field are described, with a focus on the challenges that have emerged over the past several years.
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